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Novel genomic prognostic biomarkers for dogs with cancer
BACKGROUND: Growing evidence from dogs and humans supports the abundance of mutation‐based biomarkers in tumors of dogs. Increasing the use of clinical genomic diagnostic testing now provides another powerful data source for biomarker discovery. HYPOTHESIS: Analyzed clinical outcomes in dogs with ca...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658597/ https://www.ncbi.nlm.nih.gov/pubmed/37801037 http://dx.doi.org/10.1111/jvim.16893 |
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author | Chon, Esther Sakthikumar, Sharadha Tang, Min Hamilton, Matthew J. Vaughan, Andrew Smith, Ashley Sommer, Breann Robat, Cecilia Manley, Christina Mullin, Christine Ohashi, Emi Manor, Emily Custis, James Intile, Joanne Shiu, Kai Biu Parshley, Lisa Bergman, Noelle Sheppard‐Olivares, Sabina Hafeman, Scott Wright, Zachary Haworth, David Hendricks, William Wang, Guannan |
author_facet | Chon, Esther Sakthikumar, Sharadha Tang, Min Hamilton, Matthew J. Vaughan, Andrew Smith, Ashley Sommer, Breann Robat, Cecilia Manley, Christina Mullin, Christine Ohashi, Emi Manor, Emily Custis, James Intile, Joanne Shiu, Kai Biu Parshley, Lisa Bergman, Noelle Sheppard‐Olivares, Sabina Hafeman, Scott Wright, Zachary Haworth, David Hendricks, William Wang, Guannan |
author_sort | Chon, Esther |
collection | PubMed |
description | BACKGROUND: Growing evidence from dogs and humans supports the abundance of mutation‐based biomarkers in tumors of dogs. Increasing the use of clinical genomic diagnostic testing now provides another powerful data source for biomarker discovery. HYPOTHESIS: Analyzed clinical outcomes in dogs with cancer profiled using SearchLight DNA, a cancer gene panel for dogs, to identify mutations with prognostic value. ANIMALS: A total of 127 cases of cancer in dogs were analyzed using SearchLight DNA and for which clinical outcome information was available. METHODS: Clinical data points were collected by medical record review. Variables including mutated genes, mutations, signalment, and treatment were fitted using Cox proportional hazard models to identify factors associated with progression‐free survival (PFS). The log‐rank test was used to compare PFS between patients receiving and not receiving targeted treatment before first progression. RESULTS: Combined genomic and outcomes analysis identified 336 unique mutations in 89 genes across 26 cancer types. Mutations in 6 genes (CCND1, CCND3, SMARCB1, FANCG, CDKN2A/B, and MSH6) were significantly associated with shorter PFS. Dogs that received targeted treatment before first progression (n = 45) experienced significantly longer PFS compared with those that did not (n = 82, P = .01). This significance held true for 29 dogs that received genomically informed targeted treatment compared with those that did not (P = .05). CONCLUSION AND CLINICAL IMPORTANCE: We identified novel mutations with prognostic value and demonstrate the benefit of targeted treatment across multiple cancer types. These results provide clinical evidence of the potential for genomics and precision medicine in dogs with cancer. |
format | Online Article Text |
id | pubmed-10658597 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106585972023-10-06 Novel genomic prognostic biomarkers for dogs with cancer Chon, Esther Sakthikumar, Sharadha Tang, Min Hamilton, Matthew J. Vaughan, Andrew Smith, Ashley Sommer, Breann Robat, Cecilia Manley, Christina Mullin, Christine Ohashi, Emi Manor, Emily Custis, James Intile, Joanne Shiu, Kai Biu Parshley, Lisa Bergman, Noelle Sheppard‐Olivares, Sabina Hafeman, Scott Wright, Zachary Haworth, David Hendricks, William Wang, Guannan J Vet Intern Med SMALL ANIMAL BACKGROUND: Growing evidence from dogs and humans supports the abundance of mutation‐based biomarkers in tumors of dogs. Increasing the use of clinical genomic diagnostic testing now provides another powerful data source for biomarker discovery. HYPOTHESIS: Analyzed clinical outcomes in dogs with cancer profiled using SearchLight DNA, a cancer gene panel for dogs, to identify mutations with prognostic value. ANIMALS: A total of 127 cases of cancer in dogs were analyzed using SearchLight DNA and for which clinical outcome information was available. METHODS: Clinical data points were collected by medical record review. Variables including mutated genes, mutations, signalment, and treatment were fitted using Cox proportional hazard models to identify factors associated with progression‐free survival (PFS). The log‐rank test was used to compare PFS between patients receiving and not receiving targeted treatment before first progression. RESULTS: Combined genomic and outcomes analysis identified 336 unique mutations in 89 genes across 26 cancer types. Mutations in 6 genes (CCND1, CCND3, SMARCB1, FANCG, CDKN2A/B, and MSH6) were significantly associated with shorter PFS. Dogs that received targeted treatment before first progression (n = 45) experienced significantly longer PFS compared with those that did not (n = 82, P = .01). This significance held true for 29 dogs that received genomically informed targeted treatment compared with those that did not (P = .05). CONCLUSION AND CLINICAL IMPORTANCE: We identified novel mutations with prognostic value and demonstrate the benefit of targeted treatment across multiple cancer types. These results provide clinical evidence of the potential for genomics and precision medicine in dogs with cancer. John Wiley & Sons, Inc. 2023-10-06 /pmc/articles/PMC10658597/ /pubmed/37801037 http://dx.doi.org/10.1111/jvim.16893 Text en © 2023 Vidium Animal Health and The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | SMALL ANIMAL Chon, Esther Sakthikumar, Sharadha Tang, Min Hamilton, Matthew J. Vaughan, Andrew Smith, Ashley Sommer, Breann Robat, Cecilia Manley, Christina Mullin, Christine Ohashi, Emi Manor, Emily Custis, James Intile, Joanne Shiu, Kai Biu Parshley, Lisa Bergman, Noelle Sheppard‐Olivares, Sabina Hafeman, Scott Wright, Zachary Haworth, David Hendricks, William Wang, Guannan Novel genomic prognostic biomarkers for dogs with cancer |
title | Novel genomic prognostic biomarkers for dogs with cancer |
title_full | Novel genomic prognostic biomarkers for dogs with cancer |
title_fullStr | Novel genomic prognostic biomarkers for dogs with cancer |
title_full_unstemmed | Novel genomic prognostic biomarkers for dogs with cancer |
title_short | Novel genomic prognostic biomarkers for dogs with cancer |
title_sort | novel genomic prognostic biomarkers for dogs with cancer |
topic | SMALL ANIMAL |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658597/ https://www.ncbi.nlm.nih.gov/pubmed/37801037 http://dx.doi.org/10.1111/jvim.16893 |
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